1. First-in-Human Randomized Study to Assess the Safety and Immunogenicity of an Investigational Respiratory Syncytial Virus (RSV) Vaccine Based on Chimpanzee-Adenovirus-155 Viral Vector–Expressing RSV Fusion, Nucleocapsid, and Antitermination Viral Proteins in Healthy Adults
- Author
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Esha Sarkar, Antonio Gonzalez-Lopez, Ilse Dieussaert, L Silva-Reyes, Marta Picciolato, Matthew D. Snape, Michel Janssens, Catherine de Lara, Philippe Moris, Laurence Fissette, Claire Hutchings, P Cicconi, Paul Klenerman, Amanda J. Leach, and Claire Jones
- Subjects
Adult ,0301 basic medicine ,Microbiology (medical) ,Adolescent ,Pan troglodytes ,viruses ,Respiratory Syncytial Virus Infections ,Antibodies, Viral ,medicine.disease_cause ,Virus ,Adenoviridae ,Viral vector ,Young Adult ,Viral Proteins ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Interferon ,viral vector vaccine ,Respiratory Syncytial Virus Vaccines ,medicine ,Animals ,Humans ,030212 general & internal medicine ,Nucleocapsid ,Articles and Commentaries ,first-in-human study ,biology ,business.industry ,Immunogenicity ,Virion ,RSV ,Middle Aged ,Antibodies, Neutralizing ,Virology ,Immunity, Humoral ,Transcription antitermination ,AcademicSubjects/MED00290 ,030104 developmental biology ,Infectious Diseases ,Respiratory syncytial virus (RSV) ,Respiratory Syncytial Virus, Human ,Leukocytes, Mononuclear ,biology.protein ,Antibody ,business ,medicine.drug - Abstract
Background Respiratory syncytial virus (RSV) disease is a major cause of infant morbidity and mortality. This Phase I, randomized, observer-blind, placebo- and active-controlled study evaluated an investigational vaccine against RSV (ChAd155-RSV) using the viral vector chimpanzee-adenovirus-155, encoding RSV fusion (F), nucleocapsid, and transcription antitermination proteins. Methods Healthy 18–45-year-old adults received ChAd155-RSV, a placebo, or an active control (Bexsero) at Days (D) 0 and 30. An escalation from a low dose (5 × 109 viral particles) to a high dose (5 × 1010 viral particles) occurred after the first 16 participants. Endpoints were solicited/unsolicited and serious adverse events (SAEs), biochemical/hematological parameters, cell-mediated immunogenicity by enzyme-linked immunospot, functional neutralizing antibodies, anti RSV-F immunoglobin (Ig) G, and ChAd155 neutralizing antibodies. Results There were 7 participants who received the ChAd155-RSV low dose, 31 who received the ChAd155-RSV high dose, 19 who received the placebo, and 15 who received the active control. No dose-related toxicity or attributable SAEs at the 1-year follow-up were observed. The RSV-A neutralizing antibodies geometric mean titer ratios (post/pre-immunization) following a high dose were 2.6 (D30) and 2.3 (D60). The ratio of the fold-rise (D0 to D30) in anti-F IgG over the fold-rise in RSV-A–neutralizing antibodies was 1.01. At D7 after the high dose of the study vaccine, the median frequencies of circulating B-cells secreting anti-F antibodies were 133.3/106 (IgG) and 16.7/106 (IgA) in peripheral blood mononuclear cells (PBMCs). The median frequency of RSV-F–specific interferon γ–secreting T-cells after a ChAd155-RSV high dose was 108.3/106 PBMCs at D30, with no increase after the second dose. Conclusions In adults previously naturally exposed to RSV, ChAd155-RSV generated increases in specific humoral and cellular immune responses without raising significant safety concerns. Clinical Trials Registration NCT02491463., We investigated the safety and immunogenicity of a novel chimpanzee-adenovirus-155 vaccine against respiratory syncytial virus (RSV; ChAd155-RSV). In healthy adults with previous natural RSV exposure, ChAd155-RSV generated antigen-specific humoral and cellular immune responses without raising significant safety concerns.
- Published
- 2019